The immunotoxin anti-B4/blocked ricin was administered safely in Phase I trials to pts. with relapsed/refractory B-cell lymphoma, with modest evidence of antitumor activity. This protocol attempts to develop a regimen with increased activity. Drs. Fogler and Pearson of FCRDC demonstrated, in vivo synergy between IFN-alpha and each of 2 immunotoxins, both of which recognized antigens present in the target cells. Also, in vivo, IFN-alpha in non-cytotoxic concentrations potentiated immunotoxin-induced inhibition of tumor cell protein synthesis by an as yet undetermined mechanism. Subsequent in vivo work demonstrated similar results using anti-B4bR as the immunotoxin against lymphoma cell lines in combination with IFN-alpha. The objectives of this study are: 1) to evaluate the clinical toxicity and determine the MTD of IFN-alpha and anti-B4bR in an outpatient regimen; 2) to observe any antitumor responses which occur with the combination and, 3) to characterize the host immune response to the combination of anti-B4bR and IFN-alpha. Pts. receive anti-B4bR beginning at 30 mcg/kg (lean body mass)/d by continuous infusion by a 7-day on, 7-day off schedule, with subsequent dose escalation to 35 mcg/kg/d. IFN-alpha is administered by daily SQ injection, at doses of 0.75-6.0 million units/m2/d. Pts. with relapsed/resistant NHL are eligible. After 28 days treatment, pts. with acceptable toxicity, some evidence of antitumor activity, and no development of a host antibody response are eligible for retreatment. We plan to accrue 24 pts. to this study. So far, 11 pts. have been treated. All have received 30 mcg/kg/d of anti-B4/bR. Six--four with indolent lymphomas and 2 with large cell lymphomas--have received IFN at 0.75 mu/m2, and 5 have received 1.5 mu/m2. No antitumor responses have been observed.